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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m 2 ) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m 2 ) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene ( LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene ( MPC1) and the sphingolipid transporter-1 gene ( SPNS1 ) associated with hemoglobin levels, the transforming growth factor-beta-induced gene ( TGFBI ) and the micro-RNA 129-1 ( MIR129-1) associated with IL-6 and the granzyme B gene ( GZMB ) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873., Competing Interests: Authors MK, MR, and JL were employed by the company Randox Laboratories Ltd (RANDOX), author AK was employed by the company Fraunhofer Institute of Translational Medicine and Pharmacology, author IS was employed by the company Chios Mastic Gum Growers Association, and authors FR and CL were employed by the company Biotechvana. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kanoni, Kumar, Amerikanou, Kurth, Stathopoulou, Bourgeois, Masson, Kannt, Cesarini, Kontoe, Milanović, Roig, Beribaka, Campolo, Jiménez-Hernández, Milošević, Llorens, Smyrnioudis, Francino, Milić, Kaliora, Trivella, Ruddock, Medić-Stojanoska, Gastaldelli, Lamont, Deloukas, Dedoussis and Visvikis-Siest.)

Introduction : Non-alcoholic fatty liver disease (NAFLD) is estimated to affect 25% of adult people worldwide. Nowadays, there is no definite treatment for NAFLD. International guidelines define an approach based on lifestyle changes, included a health alimentary regimen. The Mediterranean diet (MD) represents the gold standard in preventive medicine, probably due to the harmonic combination of many elements with antioxidant and anti-inflammatory properties. Its prescription is also recommended in patients with NAFLD. Olive oil, as part of MD, is associated with benefits on human health especially regarding the cardiovascular system, obesity, diabetes and related metabolic disorders. Areas covered : An overview of the beneficial effects of olive oil in the prevention and treatment of NAFLD is given. Expert opinion : A large body of evidence emphasizes that olive oil, used as primary source of fat in MD, may play a crucial role in the health benefits of NAFLD patients. However, there are still scarce clinical data that evaluate the direct effect of olive oil in human with NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a global problem and one of the most common liver diseases in the world. Various pharmacological and non-pharmacological therapies seem to be non-effective and the patients are often advised not to expect a positive outcome. Hence, even in the modern Western society many patients reach for traditional herbal products. Silymarin, a lipophilic extract derived from milk thistle (Silybum marianum) has been used in liver and bile disorders for centuries. Strong antifibrotic, antioxidant, antiviral and anti-inflammatory activities of silymarin joined with its metabolic effect proven in vitro make it ideal as a drug candidate in the therapy of NAFLD. Several recent randomized clinical studies have demonstrated that silymarin versus placebo significantly contributes to amelioration of the liver condition affected by NAFLD since it reduces steatosis severity, liver ballooning and fibrosis, followed by lowered aminotransferase levels in both short and long lasting therapies. Silymarin is also as efficient as an insulin sensitizer in the NAFLD therapy, but with less adverse effects. Phase III clinical trials have confirmed silymarin to be currently the best medication for the NAFLD patients, but the problems associated with its standardization, formulation and dosage are yet to be solved. However, green tea (Camellia sinensis) and licorice (Glycyrrhiza glabra) root extracts have also been studied in the clinical trials in the therapy of NAFLD patients. Some other herbal products, which have been tested on animals and have the potential to be used in clinical trials, are briefly summarized in this paper.